JP2019505511A5 - - Google Patents

Claims (30)

An agent capable of reducing the activity or expression of a therapeutically effective amount of CD84 for the treatment of a malignancy associated with T cell exhaustion (excluding B cell malignancies) in a subject. An agent capable of reducing the activity or expression of a therapeutically effective amount of CD84 for the treatment of an autoimmune or inflammatory disease in a subject . The agent according to claim 1, wherein the malignant disease is a solid tumor , a T-cell malignant tumor, or a myeloid malignant tumor . The solid tumor, melanoma, lung cancer, renal cell carcinoma, prostate cancer, breast cancer, ovarian cancer, head and neck cancer, colon adenocarcinoma, fibrosarcoma, cervical cancer, esophagus cancer, rectal cancer, oral cancer, liver cancer, And the medicament of claim 3 , wherein the medicament is selected from the group consisting of pancreatic cancer. 3. The medicament according to claim 2 , wherein the autoimmune disease or inflammatory disease is selected from the group consisting of multiple sclerosis, ulcerative colitis, Crohn's disease, arthritis, and lupus. The drug according to claim 2 , wherein the autoimmune disease or inflammatory disease is chronic. The drug according to claim 2 , wherein the autoimmune disease or inflammatory disease is in an acute condition. Agents that can reduce the activity or expression of the CD84 is a polynucleotide, agents according to claim 1. The agent according to claim 2, wherein the agent capable of decreasing the activity or expression of CD84 is a polynucleotide agent. It said polynucleotide agent, antisense, siRNA, micro RNA, ribozyme, and is selected from the group consisting of DNA DNAzymes agent according to any one of claims 8 or 9. An agent is an antibody that can reduce the activity or expression of the CD84, agent according to claim 1.   The agent according to claim 2, wherein the agent capable of decreasing the activity or expression of CD84 is an antibody. 13. The agent according to any of claims 11 or 12 , wherein said antibody binds to at least one epitope of the extracellular portion of said CD84. The agent according to any one of claims 11 to 13 , wherein the antibody is a CD84 neutralizing antibody. The agent capable of decreasing the activity or expression of CD84 is programmed cell death ligand 1 (PD-L1), programmed cell death 1 (PD-1), or cytotoxic T lymphocyte antigen-4 on the T cell. (CTLA-4), lymphocyte activation gene 3 (Lag-3), is intended to downregulate any one activity or expression of the killer cell lectin-like receptor G1 (KLRG1), and / or 2B4 The drug according to claim 1. The therapeutically effective amount an agent that can reduce the activity or expression of CD84 of the IL-2 by T cells, IL-4, production of IFN [gamma], and / or said T cell exhaustion associated with increased expression of CD107 it is intended to reverse the drug according to claim 1. A therapeutically effective amount of an agent capable of decreasing the activity or expression of SLAMF1 (except for an agent capable of decreasing the activity or expression of CD84) for the treatment of a malignancy associated with T cell exhaustion in a subject . The malignancy is a B cell malignancy, agent according to claim 17. The B cell malignancy is Hodgkin's lymphoma, non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, B-cell chronic lymphocytic leukemia (B-CLL) / chronic lymphocytic leukemia (CLL), chronic lymphocytic leukemia / Small lymphocytic lymphoma, chronic myeloid leukemia (CML), extranodal marginal zone B-cell lymphoma-mucosa-associated lymphoid tissue lymphoma, follicular lymphoma, mantle cell lymphoma, nodal marginal zone B-cell lymphoma, Burkitt Lymphoma, hairy cell leukemia, primary central nervous system lymphoma, splenic marginal zone B cell lymphoma, lymphocyte plasma cell lymphoma, mediastinal primary B cell lymphoma, multiple myeloma, acute lymphocytic leukemia (ALL), Acute lymphoblastic pre-B-cell leukemia, plasma cell leukemia, pre-B-cell leukemia, early pre-B-cell leukemia, and pre-B acute lymphoblastoid leukemia It is selected from the group consisting of disease, agent according to claim 18. Agents that can reduce the activity or expression of the SLAMF1 is a polynucleotide, an agent of claim 17. 21. The agent of claim 20 , wherein said polynucleotide agent is selected from the group consisting of antisense, siRNA, microRNA, ribozyme, and DNAzyme. Wherein the agent capable of reducing the activity or expression of SLAMF1 is SLAMF1 antibody, agent according to claim 17. The agent capable of decreasing the activity or expression of the SLAMF1 is a programmed cell death ligand 1 (PD-L1), a programmed cell death 1 (PD-1), a cytotoxic T lymphocyte antigen-4 on the T cell. (CTLA-4), lymphocyte activation gene 3 (Lag-3), is killer cell lectin-like receptor G1 (KLRG1), and / or the activity or expression of 2B4 as to downregulate, claim 17 Drugs . Agent capable of reducing the therapeutically effective amount of activity or expression of SLAMF1 is, the T cells with IL-2, IL-4, the T cell exhaustion associated with increased expression of production and / or CD107 of IFNγ 18. The medicament according to claim 17 , which is retrograde. Chemotherapeutics, further comprising the use of an antibody immunotherapy, and / or radiation therapy, agent according to claim 1. 3. The agent of claim 2, further comprising the use of a chemotherapeutic agent, antibody immunotherapy, and / or radiation therapy . 18. The agent of claim 17, further comprising the use of a chemotherapeutic agent, antibody immunotherapy, and / or radiation therapy. Wherein the subject is a human subject, the drug according to claim 1. 3. The method of claim 2, wherein the subject is a human subject . 18. The method of claim 17, wherein the subject is a human subject.